I. Field of the Invention
The invention relates generally to a device and method for dispensing two discrete, chemically reactive components, such as fibrinogen and thrombin as either a convergent spray or in droplet form. More specifically, the instant invention is directed to a spraying apparatus and method for dispensing fibrin sealant containing particles in either spray or droplet form, to tissues, organs, wound sites, or prosthetic devices.
II. Description of Related Art
Fibrinogen mixed with thrombin forms fibrin, a unique biomaterial. In circulating blood, fibrin is critical for establishing normal hemostasis. The clinical utility of virally inactivated fibrin glue from pooled blood plasma is based upon its ability to effectively induce hemostasis and tissue bonding, in addition to being biodegradable and generally non-immunogenic.
Fibrin glue is formed by mixing two components, human fibrinogen (or a source of fibrinogen, such as freeze-dried plasma protein concentrate of fibrinogen/factor XIII) and an activating enzyme such as thrombin. Prior to use, the lyophilized protein concentrates are conventionally solubilized by adding water. Alternately, these components may be stored frozen and thawed prior to use. Thrombin-induced activation of fibrinogen results in the formation of fibrin. Factor XIII and calcium participate in the cross-linking and stabilization of fibrin to become a tight mesh of polymeric fibrin glue. Applied to tissue, the fibrin clot adheres to the site of application. The rate of coagulation and mechanical properties of the clot are dependent on the concentration of fibrinogen as well as thrombin. Traditional fibrin glue preparations are described in International Application No. WO93/05067 to Baxter International, Inc.; WO92/13495 to Fibratek, Inc.; and U.S. Pat. No. 5,607,694, (Marx, G., Biologic Bioadhesive Compositions Containing Fibrin Glue and Liposomes, Methods of Preparation and Use, Issued Jul. 29, 1997 which is hereby incorporated by reference).
Fibrin can also be transformed into other potent tools for cell culturing and tissue engineering. For example, fibrin has been described as a permeable, visco-elastic matrix useful for organ cultures (Marx G, Methods for Tissue Embedding and Tissue Culturing, U.S. Pat. No. 5,411,885 issued May 2, 1995 which is hereby incorporated by reference). Based on fibrin's positive interactions with numerous cell types, fibrin microbeads (FMB) have been developed as a cell-culture matrix useful for culturing many types of mesenchymal cells to high density (Gorodetsky, R., et al. J. Lab. Clin. Med. 131: 269-280 (1998) and Marx G, et al., Fibrin Microbeads Prepared from Fibrinogen, Thrombin and Factor XIII, U.S. Pat. No. 6,150,505, issued Nov. 21, 2000, which is hereby incorporated by reference). When cells bound to FMB suspended in fibrinogen are applied to tissue, the result is like a “liquid tissue” which may be used for regenerating skin, bone, and other tissue in situ.
However, because fibrinogen and thrombin are mutually reactive, have different viscosities, react efficiently with each other according to precise ratios, and are relatively precious commodities, complicated fibrin applicators have been developed that attempt, to varying degrees, and with limited success to address the need for an applicator that accommodates these characteristics.
Furthermore, the delivery of FMB or particles suspended within fibrinogen has proven particularly difficult. Given the several potential uses of FMB including as drug delivery systems, as vehicles for growing and transplanting cultured cells, and to promote wound healing, the incorporation of FMB delivery with the convergent application of the two components of fibrin glue requires an applicator that can deliver particles in suspension with the same accuracy and reliability as fibrinogen or thrombin alone. Such fibrin applicators are still lacking.
A few types of dual-channel applicators have been developed to deliver fibrin glue. Most designs have been based on a dual-syringe system wherein needles are used to extract the fibrinogen and thrombin solutions from vials. The vials and needles are discarded, and the loaded syringes are assembled into a unit docked onto a dual-cannula head. The twinned syringe plungers are then actuated with the thumb, and the twin streams of fibrinogen and thrombin are expelled as liquids which mix, either within the head or external to it. U.S. Pat. No. 4,354,049 to Redl et al., and U.S. Pat. No. 5,582,596 to Fukunaga et al. are examples of such applicators. Fukunaga et al. also teaches using an additional source of air to atomize the dual-liquid channels into a spray. Some variants of this utilize a dual-point head to form an atomized spray from thumb or trigger actuated syringes. U.S. Pat. No. 5,759,171 to Coelho et al. is an example of such an approach. Other applicators are operated by mechanically actuated atomizers such as those used in conventional spray pumps. U.S. Pat. No. 4,902,281 to Avoy uses such an approach wherein two pump-style atomizers are loaded with fibrinogen and thrombin and convergently aimed.
These approaches tend to suffer from clogging or the inability to deliver suspended particles. Also, the applicators of the prior art suffer from inconvenient loading, leakage, and inadequate mechanical control of delivery volume.
Still other designs utilize a positive gas and vacuum pressure to actuate or augment the delivery mechanism such as U.S. Pat. Nos. 6,007,515 and 6,063,055 to Epstein et al. Some designs rely upon a source of compressed gas to draw the fibrinogen and thrombin from separate reservoirs using the Bernoulli principle such as U.S. Pat. No. 6,059,749 to Marx. These designs also suffer from inconvenience of loading reservoirs and are highly complex from the standpoint of having many parts or circuitous fluid pathways that may not be appropriate for delivering very viscous solutions, or solutions containing suspended particles such as FMB.
Therefore, what is needed is a mechanically simple applicator with unhindered liquid pathways for efficiently delivering precise ratios of fibrinogen and thrombin with suspended particles to form on surface or internal wounds, a fibrin matrix containing such particles.